The principal objective of this project is to determine the effect that exposure of the lung to specific antigen has on bronchopulmonary function in the immunologically-sensitized dog. The project is based upon previous studies in sensitized animals and combines the use of physiologic, pharmacologic and biochemical approaches to investigate the mechanisms through which these changes in airway function occur. Our working hypothesis is that repeated antigen exposure pre-disposes sensitized animals to exhibit the late asthmatic response and to develop non-specific airways hyperreactivity by altering the profile of mediators, specifically those derived from arachidonic acid (i.e. eicosanoids), which are synthesized within the airway tissues. Whether this alteration is due to changes in metabolism within existing airway cells or due to the antigen-induced influx on new cells, will be investigated. Specifically, the research will a) determine the role of eicosanoids and other mediators in the development of the late asthmatic reponse and investigate the relationship between the immediate and late response, b) determine the influence of repeated antigen exposure on late phase physiology, incidence and stimulus-dependency, c) determine the effects of single and repeated antigen exposure on the migration of mast cells to the airways and evaluate the pathophysiologic consequences of this migration, and d) determine the effects of repeated antigen exposure on the development of non-specific airways hyperreactivity and investigate the role of specific mediators in its development. The proposed studies represent a multidisciplined approach to investigating the influence of antigen exposure on lung function in that they utilize a variety of proven techniques to correlate changes in physiologic function with underlying cellular and biochemical mechanisms. It is anticipated that these studies will provide useful new information about pathophysiologic processes in airways of the allergic lung.